Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 22 for:    Rituxan | Granulomatosis with Polyangiitis
Previous Study | Return to List | Next Study

A Phase IIa Study of Intravenous Rituximab in Pediatric Participants With Severe Granulomatosis With Polyangiitis (Wegener's) or Microscopic Polyangiitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01750697
Recruitment Status : Completed
First Posted : December 17, 2012
Results First Posted : June 26, 2019
Last Update Posted : June 26, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Granulomatosis With Polyangiitis
Intervention Drug: Rituximab
Enrollment 25
Recruitment Details A total of 25 participants were enrolled in the study over a 3.5 year period from 11 sites across the United Kingdom, Italy, Serbia, Turkey, Canada and the United States.
Pre-assignment Details The screening visit occurred up to 28 days prior to the Day 1 baseline visit. Following successful screening, eligible participants entered the 6 month Remission Induction Phase of the study.
Arm/Group Title Rituximab
Hide Arm/Group Description Participants received rituximab as an intravenous (IV) infusion of 375 milligrams per meter squared (mg/m^2) once a week on Days 1, 8, 15 and 22 during the Remission Induction Phase (Day 1 (baseline) to Month 6) and were followed for a minimum of 18 months (maximum 4.5yrs) during the Follow-up Phase until the Common-closeout (CCO))
Period Title: Overall Study
Started [1] 25
Completed [1] 25
Follow-up Phase [2] 24 [3]
Completed [4] 16 [5]
Not Completed 9
Reason Not Completed
Transferred Back to Local Hospital             1
Physician and Family Decision             1
Transferred to Adult Services             5
Physician Decision             1
Withdrawal by Subject             1
[1]
Remission Induction Phase (Day 1 to Month 6)
[2]
(Month 6 to Month 18)
[3]
Completed required follow-up
[4]
Completed until CCO (Month 18 up to 4.5 years)
[5]
Completed to CCO. 6 participants entered Extended Safety Follow-up, 10 participants completed Study.
Arm/Group Title Rituximab
Hide Arm/Group Description Participants received rituximab as an intravenous (IV) infusion of 375 milligrams per meter squared (mg/m^2) once a week on Days 1, 8, 15 and 22 during the Remission Induction Phase (Day 1 (baseline) to Month 6) and were followed for a minimum of 18 months (maximum 4.5yrs) during the Follow-up Phase until the Common-closeout (CCO))
Overall Number of Baseline Participants 25
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants
13.4  (2.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Female
20
  80.0%
Male
5
  20.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 25 participants
Asian 4
Black or African American 1
White 17
Multiple 1
Other 2
1.Primary Outcome
Title Percentage of Participants With Adverse Events (AEs), Including Serious AEs
Hide Description An AE is any unfavourable and unintended sign (including abnormal laboratory finding), symptom, or disease temporarily associated with the use of a study drug, whether or not considered related to the study drug. A SAE is any experience that results in death, is life-threatening, requires in-patient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is medically significant.
Time Frame Baseline (Day 1) up to last visit (1.5-5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least part of one infusion of rituximab.
Arm/Group Title Remission Induction Phase (up to 6 Mos.) Rituximab Overall Follow-up Phase (up to 4.5 Yrs) Rituximab
Hide Arm/Group Description:
Participants received rituximab as an intravenous (IV) infusion of 375 milligrams per metre squared (mg/m^2) once a week on Days 1, 8, 15 and 22 during Remission Induction Phase (Day 1 (baseline) to Month 6)
Participants who received rituximab during the Remission Induction Phase were followed for a minimum of 18 months during the Follow-up Phase and could receive additional rituximab or other treatments for GPA/MPA (Day 1 (baseline) up to 4.5 yrs)
Overall Number of Participants Analyzed 25 25
Measure Type: Number
Unit of Measure: percentage of participants
Percentage of Participants with AEs 100 100
Percentage of Participants with SAEs 28 48
2.Primary Outcome
Title Pharmacokinetics: Rituximab Clearance (CL)
Hide Description

CL is a quantitative measure of the rate at which a drug substance is removed from the body. The following allometric scaling equation was used for the estimation of CL in children:

CL= qCL X (BSA/1.9) 0.92 X 1.31*ADA

where qCL is a typical value of clearance in millilitres per day (mL/day) for a typical participant (i.e., Body Surface Area (BSA) of 1.9 m^2 and absence of anti-rituximab antibodies (ADA)) and is equal to 258 mL/day; BSA is in m^2 and ADA is 1 when anti-rituximab antibodies are present (0 otherwise). The allometric scaling factor was 0.92. CL was calculated in millilitres per day (mL/day).

Time Frame From Day 1 to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis population included all participants in the safety population who provided at least one evaluable PK sample.
Arm/Group Title Rituximab (Experimental)
Hide Arm/Group Description:
Participants received rituximab as an intravenous (IV) infusion of 375 milligrams per meter squared (mg/m^2) once a week on Days 1, 8, 15 and 22 during the Remission Induction Phase (Day 1 (baseline) to Month 6) and were followed for a minimum of 18 months (maximum 4.5yrs) during the Follow-up Phase until the Common-closeout (CCO))
Overall Number of Participants Analyzed 25
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mL/day
204
(0.414%)
3.Primary Outcome
Title Pharmacokinetics: Volume of Distribution (Vd) of Rituximab
Hide Description Vd is defined as the theoretical central volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vd was calculated in millilitres (mL).
Time Frame From Day 1 to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis population included all participants in the safety population who provided at least one evaluable PK sample.
Arm/Group Title Rituximab (Experimental)
Hide Arm/Group Description:
Participants received rituximab as an intravenous (IV) infusion of 375 milligrams per meter squared (mg/m^2) once a week on Days 1, 8, 15 and 22 during the Remission Induction Phase (Day 1 (baseline) to Month 6) and were followed for a minimum of 18 months (maximum 4.5yrs) during the Follow-up Phase until the Common-closeout (CCO))
Overall Number of Participants Analyzed 25
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mL
2220
(0.212%)
4.Secondary Outcome
Title Pharmacokinetics: Area Under the Concentration-Time Curve From Time 0 to 180 Days (AUC-180) of Rituximab
Hide Description The AUC0-180 is a measure of the plasma concentration of rituximab over time. The AUC0-180 was calculated in micrograms per millilitres times day (mcg/mL*day).
Time Frame From Day 1 to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis population included all participants in the safety population who provided at least one evaluable PK sample.
Arm/Group Title Rituximab (Experimental)
Hide Arm/Group Description:
Participants received rituximab as an intravenous (IV) infusion of 375 milligrams per meter squared (mg/m^2) once a week on Days 1, 8, 15 and 22 during the Remission Induction Phase (Day 1 (baseline) to Month 6) and were followed for a minimum of 18 months (maximum 4.5yrs) during the Follow-up Phase until the Common-closeout (CCO))
Overall Number of Participants Analyzed 25
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL*day
10120
(0.42%)
5.Secondary Outcome
Title Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Rituximab
Hide Description Cmax is the maximum observed plasma rituximab concentration. Cmax was assessed at each visit following 1st, 2nd, 3rd, and 4th IV dose of rituximab 375 mg/m^2 on Days 1, 8, 15, and 22. Cmax was calculated in micrograms per millilitre (mcg/mL).
Time Frame From Day 1 to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis population included all participants in the safety population who provided at least one evaluable PK sample.
Arm/Group Title Rituximab (Experimental)
Hide Arm/Group Description:
Participants received rituximab as an intravenous (IV) infusion of 375 milligrams per meter squared (mg/m^2) once a week on Days 1, 8, 15 and 22 during the Remission Induction Phase (Day 1 (baseline) to Month 6) and were followed for a minimum of 18 months (maximum 4.5yrs) during the Follow-up Phase until the Common-closeout (CCO))
Overall Number of Participants Analyzed 25
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
1st Dose
230
(0.166%)
2nd Dose
305
(0.181%)
3rd Dose
353
(0.183%)
4th Dose
378
(0.174%)
Time Frame Up to approximately 5 years
Adverse Event Reporting Description The safety population included all participants who received at least part of one infusion of rituximab.
 
Arm/Group Title Remission Induction Phase: Rituximab Overall Follow-up Phase: Rituximab
Hide Arm/Group Description Participants received rituximab as an IV infusion of 375 mg/m^2 once a week on Days 1, 8, 15 and 22 during Remission Induction Phase (Day 1 (baseline) to Month 6) Participants who received rituximab during the remission induction phase were followed for a minimum of 18 months during the follow-up phase and could receive additional rituximab or other treatments for GPA/MPA (Day 1 (baseline) up to 4.5 yrs)
All-Cause Mortality
Remission Induction Phase: Rituximab Overall Follow-up Phase: Rituximab
Affected / at Risk (%) Affected / at Risk (%)
Total   0/25 (0.00%)   0/25 (0.00%) 
Hide Serious Adverse Events
Remission Induction Phase: Rituximab Overall Follow-up Phase: Rituximab
Affected / at Risk (%) Affected / at Risk (%)
Total   7/25 (28.00%)   12/25 (48.00%) 
Blood and lymphatic system disorders     
Sickle cell anaemia with crisis  1  0/25 (0.00%)  1/25 (4.00%) 
Congenital, familial and genetic disorders     
Sickle cell anaemia  1  0/25 (0.00%)  1/25 (4.00%) 
Gastrointestinal disorders     
Pancreatitis  1  0/25 (0.00%)  1/25 (4.00%) 
Immune system disorders     
Anti-neutrophil cytoplasmic antibody positive vasculitis  1  0/25 (0.00%)  1/25 (4.00%) 
Infections and infestations     
Device related sepsis  1  0/25 (0.00%)  1/25 (4.00%) 
Eye infection bacterial  1  0/25 (0.00%)  1/25 (4.00%) 
Gastroenteritis norovirus  1  0/25 (0.00%)  1/25 (4.00%) 
Gastroenteritis viral  1  1/25 (4.00%)  1/25 (4.00%) 
Influenza  1  1/25 (4.00%)  2/25 (8.00%) 
Lower respiratory tract infection  1  1/25 (4.00%)  2/25 (8.00%) 
Sinusitis  1  0/25 (0.00%)  1/25 (4.00%) 
Injury, poisoning and procedural complications     
Infusion related reaction  1  1/25 (4.00%)  1/25 (4.00%) 
Musculoskeletal and connective tissue disorders     
Myopathy  1  1/25 (4.00%)  1/25 (4.00%) 
Nervous system disorders     
Seizure  1  0/25 (0.00%)  1/25 (4.00%) 
Psychiatric disorders     
Suicidal ideation  1  0/25 (0.00%)  1/25 (4.00%) 
Respiratory, thoracic and mediastinal disorders     
Bronchostenosis  1  1/25 (4.00%)  1/25 (4.00%) 
Laryngeal obstruction  1  0/25 (0.00%)  1/25 (4.00%) 
Vascular disorders     
Granulomatosis with polyangiitis  1  2/25 (8.00%)  4/25 (16.00%) 
Vasculitis  1  1/25 (4.00%)  1/25 (4.00%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Remission Induction Phase: Rituximab Overall Follow-up Phase: Rituximab
Affected / at Risk (%) Affected / at Risk (%)
Total   22/25 (88.00%)   24/25 (96.00%) 
Blood and lymphatic system disorders     
Neutropenia  1  0/25 (0.00%)  2/25 (8.00%) 
Ear and labyrinth disorders     
Deafness unilateral  1  0/25 (0.00%)  2/25 (8.00%) 
Gastrointestinal disorders     
Abdominal pain  1  2/25 (8.00%)  3/25 (12.00%) 
Abdominal pain upper  1  3/25 (12.00%)  4/25 (16.00%) 
Constipation  1  3/25 (12.00%)  3/25 (12.00%) 
Diarrhoea  1  0/25 (0.00%)  7/25 (28.00%) 
Gastritis  1  0/25 (0.00%)  2/25 (8.00%) 
Nausea  1  4/25 (16.00%)  5/25 (20.00%) 
Vomiting  1  2/25 (8.00%)  4/25 (16.00%) 
General disorders     
Chest pain  1  2/25 (8.00%)  3/25 (12.00%) 
Non-cardiac chest pain  1  0/25 (0.00%)  2/25 (8.00%) 
Immune system disorders     
Hypogammaglobulinaemia  1  0/25 (0.00%)  3/25 (12.00%) 
Infections and infestations     
Conjunctivitis  1  2/25 (8.00%)  5/25 (20.00%) 
Ear infection  1  0/25 (0.00%)  3/25 (12.00%) 
Fungal skin infection  1  0/25 (0.00%)  2/25 (8.00%) 
Gastroenteritis  1  2/25 (8.00%)  3/25 (12.00%) 
Herpes zoster  1  0/25 (0.00%)  2/25 (8.00%) 
Influenza  1  0/25 (0.00%)  4/25 (16.00%) 
Lower respiratory tract infection  1  0/25 (0.00%)  3/25 (12.00%) 
Nasopharyngitis  1  2/25 (8.00%)  5/25 (20.00%) 
Oral herpes  1  2/25 (8.00%)  2/25 (8.00%) 
Pharyngitis  1  0/25 (0.00%)  3/25 (12.00%) 
Pneumonia  1  0/25 (0.00%)  2/25 (8.00%) 
Sinusitis  1  0/25 (0.00%)  3/25 (12.00%) 
Tooth infection  1  0/25 (0.00%)  2/25 (8.00%) 
Upper respiratory tract infection  1  4/25 (16.00%)  12/25 (48.00%) 
Urinary tract infection  1  0/25 (0.00%)  3/25 (12.00%) 
Viral upper respiratory tract infection  1  2/25 (8.00%)  4/25 (16.00%) 
Injury, poisoning and procedural complications     
Fall  1  0/25 (0.00%)  2/25 (8.00%) 
Infusion related reaction  1  14/25 (56.00%)  16/25 (64.00%) 
Skin abrasion  1  0/25 (0.00%)  2/25 (8.00%) 
Investigations     
Blood immunoglobulin G decreased  1  2/25 (8.00%)  2/25 (8.00%) 
C-reactive protein increased  1  0/25 (0.00%)  2/25 (8.00%) 
Serum ferritin decreased  1  0/25 (0.00%)  2/25 (8.00%) 
Metabolism and nutrition disorders     
Iron deficiency  1  0/25 (0.00%)  2/25 (8.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  3/25 (12.00%)  5/25 (20.00%) 
Back pain  1  3/25 (12.00%)  5/25 (20.00%) 
Musculoskeletal chest pain  1  0/25 (0.00%)  2/25 (8.00%) 
Pain in extremity  1  2/25 (8.00%)  4/25 (16.00%) 
Nervous system disorders     
Headache  1  4/25 (16.00%)  9/25 (36.00%) 
Migraine  1  0/25 (0.00%)  3/25 (12.00%) 
Tremor  1  2/25 (8.00%)  2/25 (8.00%) 
Psychiatric disorders     
Depression  1  0/25 (0.00%)  2/25 (8.00%) 
Insomnia  1  0/25 (0.00%)  2/25 (8.00%) 
Reproductive system and breast disorders     
Amenorrhoea  1  2/25 (8.00%)  2/25 (8.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  3/25 (12.00%)  6/25 (24.00%) 
Dyspnoea  1  0/25 (0.00%)  2/25 (8.00%) 
Epistaxis  1  3/25 (12.00%)  7/25 (28.00%) 
Oropharyngeal pain  1  0/25 (0.00%)  2/25 (8.00%) 
Skin and subcutaneous tissue disorders     
Erythema  1  0/25 (0.00%)  3/25 (12.00%) 
Pruritus  1  2/25 (8.00%)  2/25 (8.00%) 
Purpura  1  0/25 (0.00%)  2/25 (8.00%) 
Rash  1  0/25 (0.00%)  2/25 (8.00%) 
Rash erythematous  1  2/25 (8.00%)  2/25 (8.00%) 
Skin striae  1  2/25 (8.00%)  2/25 (8.00%) 
Vascular disorders     
Granulomatosis with polyangiitis  1  0/25 (0.00%)  2/25 (8.00%) 
Hypertension  1  2/25 (8.00%)  3/25 (12.00%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
After Month 6, participants could receive treatment for GPA/MPA in accordance with local standard of care, and this could include additional rituximab infusions and/or other immunosuppressive therapies. Low participant numbers (e.g., 1 subject = 4%).
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01750697    
Other Study ID Numbers: WA25615
2012-002062-13 ( EudraCT Number )
First Submitted: December 13, 2012
First Posted: December 17, 2012
Results First Submitted: May 3, 2019
Results First Posted: June 26, 2019
Last Update Posted: June 26, 2019